At an early age he was acclaimed for his broad learning in both Jewish and Italian culture, as well as in general sciences and languages. By the time he was fifteen he ceased formal education and established a mystical group in his home.
When he was twenty, he experienced visions of a heavenly mentor who “revealed" to him celestial secrets that he wrote down; most of these works were lost. He conveyed these doctrines to his circle of intimates to whom he indicated that he might be the Messiah, seeing himself as a reincarnation of Moses. He also indulged in “practical Kabbalah” (magical practices) to attain supernatural powers.
When this became known to the local rabbis, they were alarmed, especially as the memory of the bitter experience of the pseudomessianic movement led by Shabbetai Tzevi was still strong. Under these pressures Luzzatto agreed in 1730 to conceal his esoteric writings and not to convey his kabbalistic views to others.
However, he continued to be persecuted and left Italy for Amsterdam, where he earned a living as a diamond polisher. Here too the local rabbis opposed him and put his writings under a ban. He refrained from public expression of his views but he enjoyed a measure of tranquility and was able to write his ethical work Mesillat Yesharim (“Path of the Upright”). In 1743 he moved to Eretz Israel, probably out of messianic motivations. He settled in Safed, where his wife and son died in a plague. He moved to Acre, where he himself died a year later.
His chief literary activity was the composition of three plays: The Story of Samson, in which his deep identification with the hero may stem from messianic reasons; Tower of Strength, influenced by contemporary Italian pastoral drama, which some see as a kabbalistic allegory; and Praise to the Righteous, which reflects his own experiences as a persecuted victim. These dramas are secular works, with a biblical Hebrew style.
He also wrote on philosophy, logic, rhetoric, polemics, and Talmudic dialectics. Path of the Upright became one of the most popular of all Jewish ethical works. It expounds ascending grades of ethical conduct and was studied for moral and religious self-discipline.